Drug Administration Research Articles

Comparison of Real-World On-Label Treatment Persistence in Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Tumor Necrosis Factor Inhibitors.

Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis). Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified inthe IQVIA PharMetrics® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts. The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3-12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p<0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p<0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort. This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi.

Nanocellulose-alginate composite beads for improving Ciprofloxacin bioavailability

Nanocellulose is a potential material utilized in numerous biomedical applications. However, its hydrophilic characteristic and uncontrolled encapsulated drug release hinders nanocellulose uses in oral drug administration. Thus, this work developed novel nanocellulose/alginate composite (CNC/Alg) beads for oral delivery and bioavailability enhancement of a model drug, Ciprofloxacin (CIP). CNC was green synthesized employing electrolysis process from sugarcane bagasse. CNC/Alg beads were formulated by dropwise adding CNC-Alg mixture in CaCl2 solution at room temperature. CIP was incorporated into CNC/Alg beads by adsorption technique. X-ray diffractometry and Fourier-transform infrared spectra images showed that the beads were effectively produced with high crystallinity of 75.5 %, and the typical bond of cellulose and alginate. Within 4 h of adsorption, CIP loading efficiency reached 45.27 %, with 87.2 % molecules in the zwitterionic state. The adsorption followed Elovich and pseudo-second-order models, indicating a multi-mechanism including both physical and chemical adsorptions. Importantly, in gastrointestinal tract, the beads could protect CIP from acidic stomach environment while releasing it sustainably in simulated intestinal condition (75.05 %). The beads also showed strong antibacterial activity against both Gram(−) and Gram(+) bacteria, as evidenced by low IC50 and minimum inhibitory concentration values. Finally, CNC/Alg beads could improve CIP bioavailability for effective oral drug delivery route.

Signal mining of adverse reactions in the antiemetic drug ondansetron during pregnancy:A Real-World analysis of the FDA adverse Event Reporting System (FAERS)

ABSTRACT Background The aim of this study is to assess the risks associated with the use of ondansetron in pregnant women in real-world based on the Food and Drug Administration adverse Event Reporting System (FAERS). Methods The FAERS data from the 2017Q1 to the 2023Q1, which was used by the ratio-of-reporting (ROR) and Bayesian confidence interval progressive neural network (BCPNN) to assess the safety of ondansetron in pregnancy. Results A total of 15,727 pregnancy population reports were reported, with a total of 1,064 reports of adverse reactions with ondansetron as the primary suspected drug. Ondansetron was involved in a total of 10 system organ classifications (SOCs) of signal generation, and the top three signal intensities were Congenital, familial and genetic disorders (ROR=19.1, ROR025=17.03; IC=1.23, IC025=1.16), Ear and labyrinth disorders (ROR=17.11, ROR025=12.46; IC=1.22, IC025=1.03), and Cardiac disorders (ROR=9.48, ROR025=8.38; IC=1.12, IC025=1.03); signals of adverse reactions obtained of 216, of which the main ones were Anhedonia (IC=1.34, IC025=1.08), Injury (IC=1.34, IC025=1.19), Left-to-right cardiac shunt (IC=1.33, IC025=1.05). Conclusion The adverse reactions of Ondansetron involve multiple systems and organs, which should cause clinical vigilance. However, due to the limitations of the data, the causal relationship and risk level of adverse reactions cannot be accurately inferred.

A Human Feedback Strategy for Photoresponsive Molecules in Drug Delivery: Utilizing GPT-2 and Time-Dependent Density Functional Theory Calculations

Photoresponsive drug delivery stands as a pivotal frontier in smart drug administration, leveraging the non-invasive, stable, and finely tunable nature of light-triggered methodologies. The generative pre-trained transformer (GPT) has been employed to generate molecular structures. In our study, we harnessed GPT-2 on the QM7b dataset to refine a UV-GPT model with adapters, enabling the generation of molecules responsive to UV light excitation. Utilizing the Coulomb matrix as a molecular descriptor, we predicted the excitation wavelengths of these molecules. Furthermore, we validated the excited state properties through quantum chemical simulations. Based on the results of these calculations, we summarized some tips for chemical structures and integrated them into the alignment of large-scale language models within the reinforcement learning from human feedback (RLHF) framework. The synergy of these findings underscores the successful application of GPT technology in this critical domain.

In silico study suggests potential drugs that target CD151 to treat breast cancer and lioblastoma.

Recently tetraspanin CD151 has been identified as an important biological target involved in metastatic processes which include cell adhesion, tumor progression processes, and so forth in different types of cancers, such as breast cancer and glioblastoma. This in Silico study considered 1603 compounds from the Food and Drug Administration database, after performing an ADMET analysis; we selected 853 ligands, which were used for docking analysis. The most promising ligands were selected from docking studies, based on two criteria: (a) showed lowest affinity to the CD151 protein and (b) they interact with the QRD motif, located in the second extracellular loop. Furthermore, we investigate the stability of the protein-ligand complexes through MD simulations as well as free energy MM-PBSA calculations. From these results, loperamide and glipizide were identified as the best evaluated drugs. We suggest an in vitro analysis is needed to confirm our in silico prediction studies.

Methodology of clinical trials on sodium-glucose cotransporter 2 inhibitors registered on ClinicalTrials.gov: a cross-sectional study

Background/ObjectiveThe research on sodium-glucose cotransporter 2 (SGLT2) inhibitors has been increasing rapidly in the last decade, as well as indications for their use. This study aimed to analyze the methodological characteristics of clinical trials on SGLT2 inhibitors registered on ClinicalTrials.gov.DesignWe conducted a cross-sectional study of trials on SGLT2 inhibitors registered on ClinicalTrials.gov up to November 11, 2022. We included clinical trials that tested SGLT2 inhibitors for any clinical condition, as a single or combined SGLT2 therapy, compared to any other medication or placebo and mapped their characteristics.ResultsWe identified 1102 eligible trials on 14 different SGLT2 inhibitors. The first trial registration was in 2005. There were 993 (90%) interventional and 109 (10%) observational trials. Most trials were in Phase 1 (29%), Phase 3 (23%), or Phase 4 (24%). Interventional trials were mostly randomized (85%); almost half of them did not use masking (44%). Trials on empagliflozin, dapagliflozin, and canagliflozin accounted for 75% of all trials. More than 60% of trials included patients with diabetes mellitus, 13% included only healthy subjects, and 12% included patients with heart diseases. Overall, these trials included more than 9.5 million participants (~ 312,000 of which in interventional studies). Almost 65% of all clinical trials were industry-funded. Most trials were completed (60%) and 35% of those reported results. For trials that are obligated to report results by the Food and Drugs Administration (FDA), 88% of them did so. Trials fully or partially funded by industry more frequently published results compared to non-industry funded trials (46.1% vs. 11.2%; p < 0.001).ConclusionsThe number of registered trials on SGLT2 inhibitors is increasing progressively along with expanding indications for its use, shifting from diabetes mellitus to cardiovascular and renal diseases. Public reporting of trial results improved with time but remains suboptimal.

Increase in the Expression of Glucose Transporter 2 (GLUT2) on the Peripheral Blood Insulin-Producing Cells (PB-IPC) in Type 1 Diabetic Patients after Receiving Stem Cell Educator Therapy

Multicenter international clinical trials demonstrated the clinical safety and efficacy by using stem cell educator therapy to treat type 1 diabetes (T1D) and other autoimmune diseases. Previous studies characterized the peripheral blood insulin-producing cells (PB-IPC) from healthy donors with high potential to give rise to insulin-producing cells. PB-IPC displayed the molecular marker glucose transporter 2 (GLUT2), contributing to the glucose transport and sensing. To improve the clinical efficacy of stem cell educator therapy in the restoration of islet β-cell function, we explored the GLUT2 expression on PB-IPC in recent onset and longstanding T1D patients. In the Food and Drug Administration (FDA)-approved phase 2 clinical studies, patients received one treatment with the stem cell educator therapy. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry analysis of PB-IPC and other immune markers before and after the treatment with stem cell educator therapy. Flow cytometry revealed that both recent onset and longstanding T1D patients displayed very low levels of GLUT2 on PB-IPC. After the treatment with stem cell educator therapy, the percentages of GLUT2+CD45RO+ PB-IPC were markedly increased in these T1D subjects. Notably, we found that T1D patients shared common clinical features with patients with other autoimmune and inflammation-associated diseases, such as displaying low or no expression of GLUT2 on PB-IPC at baseline and exhibiting a high profile of the inflammatory cytokine interleukin (IL)-1β. Flow cytometry demonstrated that their GLUT2 expressions on PB-IPC were also markedly upregulated, and the levels of IL-1β-positive cells were significantly downregulated after the treatment with stem cell educator therapy. Stem cell educator therapy could upregulate the GLUT2 expression on PB-IPC and restore their function in T1D patients, leading to the improvement of clinical outcomes. The clinical data advances current understanding about the molecular mechanisms underlying the stem cell educator therapy, which can be expanded to treat patients with other autoimmune and inflammation-associated diseases.

The Food and Drug Administration's Latest Efforts to Improve Safe Use of Hydrogen Peroxide Contact Lens Solution.

The Food and Drug Administration's Latest Efforts to Improve Safe Use of Hydrogen Peroxide Contact Lens Solution.

Improving Access to Patient-Focused, Decentralized Clinical Trials Requires Streamlined Regulatory Requirements: An ASCO Research Statement.

Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.

Dapsone Use in Dermatology.

Dapsone, initially synthesized for textile dyeing, gained recognition in the 1930s for its antibacterial properties, leading to its utilization in dermatology for leprosy and dermatitis herpetiformis. Despite US Food and Drug Administration (FDA) approval for these conditions, dapsone's off-label uses have expanded, making it a valuable option in various dermatologic conditions. This review seeks to highlight the common uses of dapsone in its FDA indications and off-label indications. Diseases in which dapsone is considered first-line therapy or adjunctive therapy are reviewed, with highlights from the resources included. An overview of dapsone's pharmacokinetics, pharmacodynamics, indications, dosages, and safety profile are also reviewed. Dapsone's versatility and safety profile make it a cost-effective treatment option in dermatology, particularly for patients with limited access to specialized medications. Ongoing clinical trials are also described exploring dapsone's efficacy in novel dermatologic uses. Dapsone has been a valuable adjunctive therapy across various dermatologic conditions for years and evidence for its use continues to expand.

Refined tamoxifen administration in mice by encouraging voluntary consumption of palatable formulations

Drug administration in preclinical rodent models is essential for research and the development of novel therapies. Compassionate administration methods have been developed, but these are mostly incompatible with water-insoluble drugs such as tamoxifen or do not allow for precise timing or dosing of the drugs. For more than two decades, tamoxifen has been administered by oral gavage or injection to CreERT2–loxP gene-modified mouse models to spatiotemporally control gene expression, with the numbers of such inducible models steadily increasing in recent years. Animal-friendly procedures for accurately administering tamoxifen or other water-insoluble drugs would, therefore, have an important impact on animal welfare. On the basis of a previously published micropipette feeding protocol, we developed palatable formulations to encourage voluntary consumption of tamoxifen. We evaluated the acceptance of the new formulations by mice during training and treatment and assessed the efficacy of tamoxifen-mediated induction of CreERT2–loxP-dependent reporter genes. Both sweetened milk and syrup-based formulations encouraged mice to consume tamoxifen voluntarily, but only sweetened milk formulations were statistically noninferior to oral gavage or intraperitoneal injections in inducing CreERT2-mediated gene expression. Serum concentrations of tamoxifen metabolites, quantified using an in-house-developed cell assay, confirmed the lower efficacy of syrup- as compared to sweetened milk-based formulations. We found dosing with a micropipette to be more accurate than oral gavage or injection, with the added advantage that the method requires little training for the experimenter. The new palatable solutions encourage voluntary consumption of tamoxifen without loss of efficacy compared to oral gavage or injections and thus represent a refined administration method.

Advice to the US FDA to Allow US Pharmacopeia to Create Biological Product Specifications (BPS) to Remove Side-by-Side Analytical Comparisons of Biosimilars with Reference Products

Pharmacopeia monographs are not intended to establish biosimilarity. However, the US Food and Drug Administration (FDA) has stopped the US Pharmacopeia (USP) from creating monographs for biological drugs due to the need for side-by-side comparisons with the reference products. The USP can create Biological Product Specifications (BPS), not to be labeled as monographs, based on the analytical testing of reference products and validated test methods that will remove the need for side-by-side analytical testing of biosimilars with reference products. Scientific arguments confirm that this plan is logical and capable of creating global quality standards for biosimilars to allow their interchangeability with other biosimilars. While the regulatory agencies have waived many high-cost biosimilar tests, analytical assessment is the most sensitive test; reducing its cost will further enhance the entry of biosimilars with no clinically meaningful difference.

The effect of simulated food liquids on the surface structure and solubility of various esthetic restorations

Aims: The aim of this study is to investigate the surface roughness and solubility of restorative materials when exposed to foodstuffs in the oral environment using simulated food liquids as defined by the Food and Drug Administration. Methods: In this study, a total of four esthetic restorative materials were used: one universal compomer (Dyract XP, Dentsply), one conventional microhybrid composite (FiltekTM Z250, 3M ESPE), one nanofilled, and one high-viscosity glass ionomer cement (ChemFil Rock, Dentsply). A total of 160 samples, each 8 mm in diameter and 2 mm in thickness, were prepared using molds. The initial weights of the samples were recorded in micrograms using a precision balance to determine solubility values. Initial surface roughness values were measured using an atomic force microscope device. The samples were immersed in four different simulated food liquids (ethanol, heptane, citric acid, and distilled water) for a period of 7 days. After removal from the solutions, the samples were desiccated to a constant weight, and the second set of weights was recorded. Subsequently, the second surface roughness values were measured Results: Among the materials immersed in the simulated food solutions, ChemFil Rock exhibited the highest solubility and increase in surface roughness. Citric acid was found to be the solution that caused the highest increase in surface roughness values and solubility for this material (p

Exploring the Efficacy and Safety of Interleukin‐23 Inhibitors in Dissecting Cellulitis of the Scalp: A Comprehensive Review

ABSTRACTBackgroundDissecting cellulitis of the scalp (DCS), also known as perifolliculitis capitis abscedens et suffodiens or Hoffmann disease, is a rare chronic inflammatory scalp condition with an unknown etiology. The US Food and Drug Administration (FDA) has recently approved multiple interleukin‐23 (IL‐23) inhibitors for chronic‐plaque psoriasis, and their off‐label use has shown promise in treating various dermatological conditions, including DCS. This review assesses the efficacy and safety of IL‐23 inhibitors for DCS, aiming to support potential FDA approval for severe refractory cases.MethodsA comprehensive literature search was conducted in February 2024 using MEDLINE, PUBMED, and Google Scholar with the keywords “Dissecting cellulitis,” “DCS,” “Interleukin‐23 inhibitors,” “IL‐23,” and “Biologics.” The search focused on identifying studies reporting the use of IL‐23 inhibitors in DCS treatment.ResultsThe search identified five cases where IL‐23 inhibitors were used to treat DCS. All patients were male, aged 17–65 years, with multiple comorbidities in four cases, primarily hidradenitis suppurativa and acne conglobata. The IL‐23 inhibitors Risankizumab, Guselkumab, and Tildrakizumab were used, resulting in significant clinical improvement, near‐complete remission, and hair regrowth. Additionally, psychosocial improvements were noted in two cases, with no reported adverse effects.ConclusionIL‐23 inhibitors have shown remarkable efficacy in treating severe DCS, with significant clinical and psychosocial improvements and a favorable safety profile. These findings support the consideration of FDA approval for IL‐23 inhibitors as a treatment option for refractory DCS cases, offering hope for patients with this challenging condition.

A Systematic Review of Existing Data on Statin Use and New - Onset Type 2 Diabetes: The Need for Clear Answers

Background: The relationship between statins use and the development of new-onset type 2 diabetes mellitus (NOT2DM) has been a subject of ongoing debate and investigation. In February 2012, the Food and Drug Administration (FDA) disclosed that statin use could lead to a modest rise in glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), potentially contributing to the development of diabetes. We systematically reviewed the available evidence and summarized the impact of statin use on NOT2DM. Aims and Objectives: This systematic review aims to examine and provide a comprehensive overview of existing data relating to statin use and their association with the development of new-onset type 2 diabetes (NOT2DM). The primary objectives were to assess and explore: (1) the potential association between statin use and the development of new-onset diabetes; (2) the magnitude, extent, and incidence of new-onset diabetes due to statin use. The secondary objective was to explore the underlying mechanisms. Data Sources: PubMed, Scopus, Science Direct, Wiley, and Google Scholar and databases between January 2012 and February 2021. Data Extraction: The 2 reviewers Musa Basheer Mansour and Sara Elsheikh Ahmedana [MBM and SEA] independently assessed the qualities of the extracted studies and summarized data of the selected studies in tabulated forms for outcomes of interest and performed methodological and quality assessments based on review questions, citations, country of the study, aim, population characteristics, design, setting, sample size, sample technique, data source, measures, analysis, confounder variable and key observations for systematic review. We applied search keywords such as Statins, New-onset diabetes, Diabetes mellitus, Underlying mechanism, and incidents of diabetes. Results: A total of 66 studies were identified through database searches in the initial search, and 7 studies were included in this review. Of the 2,567,888 adult patients, 861,925 were nondiabetic patients on statin use, and 1,705,963 were diabetic on statin or non-statin users. We considered Hazard Ratios (HR), Odds Ratios (OR), and Confidence Intervals (CI) of each study for further analysis. The mean OR for three studies showed that each statin therapy resulted in a 68% increased risk of NOT2DM (OR, 1.683; 95% CI: 1.273-2.237). The significant relationship between statin use and the rising risk of NOT2DM was also confirmed by an average HR of 1.53 (95% CI: 1.2-1.7) for the remaining four studies. Recent and short-term use of statins, as well as time- and dose-dependent connections, were linked to an increased risk of NOT2DM in statin users compared to non-users. These risks were more prominent among older adults, normotensive males, hypertensive females, and individuals with low physical activity. Although no proven mechanisms were found, the possible processes are discussed. Conclusion: The systematic review found a significant level of risk of NOT2DM associated with statin use. The authors argued that the short-term diabetes risk caused by statin treatment was more prevalent among patients exposed to risk factors for diabetes. Although the precise mechanisms behind this association remain unclear, this research provides clinical practice with evidence-based guidelines. Additionally, conducting future research may be appropriate based on the gaps in knowledge identified from the results of this review.

The Effect of Wudhu Spiritual Therapy in Controlling Emotions in Patients at Risk of Violent Behavior

In the Limboto Health Centre working area, the behavioral changes of patients at risk of violent behavior were found to be that these patients had never received spiritual ablution therapy and were only given medication as prescribed or recommended. Mental disorders affect 970 million people worldwide. This study aims to determine whether ablution spiritual healing helps patients at risk of violent behavior in the Limboto Health Centre working area to control their emotions. Pre exploratory examination plan with one collection pretest-posttest configuration approach, the population of patients in danger of violent behavior in the working area of Limboto Community Group Welfare Centre, number of tests 15 people with complete examination procedures, information collected using the perception of signs and side effects sheet of patients in danger of violent behavior and tried using matched t-test measured parametric test. Results showed that before being given medication for otherworldly bathing treatment, all patients gave indications and side effects that generally appear in patients in danger of violent behavior. Still, after intercession, patients have the option to get mediation. control their feelings after being given bathing treatment given the consequences caused by paying attention to the symptoms and side effects. The p.value obtained from the paired t-test was 0.001 which is smaller than the value of 0.05. It was established in the Limboto Health Centre working area that the spiritual therapy of ablution helps patients at risk of violent behavior to control their emotions. Therefore, the health center is expected to support medical treatment to achieve more effective results in addition to using medical therapy which includes the administration of drugs

Engineering extracellular vesicles derived from lemons for delivering chemotherapeutic drug employing periostin targeting

Drug administration methods aim to reduce adverse effects and enhance the effectiveness of chemotherapy medications. Extracellular vesicles (EVs) have shown outstanding ability in drug delivery for a wide range of drugs, including chemotherapy drugs. One of the main objectives of this study was to enhance the selective delivery of doxorubicin (DOX) by utilizing modified lemon extracellular vesicles (LEV) for targeted delivery, in order to overcome breast cancer. Additionally, it aimed to further hinder both cancer cell growth and movement by disrupting periostin peptide (PN) via interaction between anti-periostin peptide (APN) and PN. The LEV was extracted from lemon juice, modified with APN onto its surface, and then DOX was loaded into the LEV-APN. The particle size and zeta potential were measured. The release study of DOX from the LEV-APN-DOX nanodrug was higher at an acidic pH 5.4 than the normal pH 7.4. The cellular uptake and cytotoxicity of the LEV-APN-DOX nanodrug were evaluated using flow cytometry analysis and the MTT method, respectively. In vivo therapeutic efficiency of the prepared nanoformulation was assessed using 4T1 tumor-bearing female BALB/c mice. Ex vivo fluorescent imaging revealed increased tumor accumulation and decreased heart clearance in LEV-APN-DOX compared to DOX. The histopathological evaluation also confirmed this result. Our findings highlight the potential of utilizing APN-modified liposomal doxorubicin to specifically target and efficiently treat breast adenocarcinoma.

Physico-chemical and bacteriological quality assessment of some selected sachet water brands produced in Gwale local government Area, Kano Nigeria

The proliferation of sachet water products has been fuelled by the rising demand for clean, safe drinking water in areas where access to potable water sources remains a challenge. Unfortunately, some of the sachet water producers fail to adhere to the standards set by regulatory agencies, resulting in potential health risk for the unsuspecting consumers. Therefore, critical investigation of the various parameters of these water products is needed to determine whether they meet the safety standards established by regulatory agencies. Thirty (30) different brands of sachet water (15 NAFDAC registered and 15 non-NAFDAC registered) were randomly collected (n=3) from producers in Gwale Local Government Area, Kano Nigeria to assess their physico-chemical and bacteriological quality. The parameters were determined using standard methods. The mean results of the temperature, pH, turbidity, conductivity, chloride and total hardness of the NAFDAC registered samples were found to be in the range of 25.9-29.7 oC, 6.8-7.2, 0.1-1.2 NTU, 11.0-41.8µs/cm,15.0-25.1 mg/L and 2.0-17.6 mg/L respectively, while for the non-NAFDAC registered samples, the mean range were found to be 25.8-30.8 oC, 6.6-8.7, 0.5-2.2 NTU, 13.6-46.8 µs/cm, 17.0 23.0mg/L and 15.8-25.3 mg/L for the same parameters respectively. These results are in compliance with the standards set by the National Agency for Food Drug Administration and Control (NAFDAC), Nigerian Industrial Standard (NIS) and World Health Organization (WHO) except pH values of 8.7 found in some non-NAFDAC registered samples which were a bit higher than the recommended limits. Some non- NAFDAC registered samples were found to contain aerobic mesophilic bacteria, though below the limit set by the aforementioned regulatory agencies. Statistically, there is significant difference (p&gt;2.326) between the NAFDAC registered and the non-NAFDAC registered samples in aerobic mesophilic bacterial count but there is no significant difference in terms of coliform count between the two groups (p&lt; 2.326). This finding highlights the need for regular microbiological monitoring so as to ensure public health safety.

Utilizing a sutureless valve for prosthetic valve endocarditis after aortic root replacement

BackgroundReoperation following aortic root replacement is associated with significantly high operative mortality. Etiologies related to infection are known to increase the operative mortality rate more than other etiologies. In such a clinical setting, a sutureless valve could lower the operative mortality by shortening the cardiac arrest and the operative time.Case presentationA 61-year-old male underwent emergent aortic root and total arch replacement with an open stent graft for acute type-A aortic dissection. A bioprosthetic valve was employed for aortic root replacement using the double-sewing ring technique. A fungal infection by Candida parapsilosis was postoperatively detected and improved with intravenous antifungal drug administration. However, he developed congestive heart failure one year later, and the blood cultures turned positive repeatedly for Candida parapsilosis. The prosthetic valve infection was suspected upon identifying vegetation on the bioprosthetic valve through transthoracic echocardiography. The computed tomography scan and operative findings confirmed that the infection was localized on the prosthetic valve. Consequently, the infected valve was removed without a vascular conduit, and a sutureless valve was implanted. The postoperative course was uneventful, without any evidence of recurrent fungal infection, and the patient was discharged on postoperative day 28.ConclusionsDeploying a sutureless valve can facilitate a more straightforward and minimally invasive redo procedure. Preoperative computed tomography can predict the valve size, which is the key to implanting a sutureless valve successfully after the modified Bentall procedure.

Drug administration via feeding tubes-a procedure that carries risks: systematic identification of critical factors based on commonly administered drugs in a cohort of stroke patients.

Drug administration via feeding tubes is considered a process with many uncertainties. This review aimed to give a comprehensive overview of data available on feeding tube application and to carry out risk assessments for drug substances commonly administered to stroke patients. Drugs frequently administered via feeding tubes were identified through a retrospective analysis of discharge letters from a stroke unit. Physicochemical, pharmacokinetic, and stability properties of these drugs and data on drug-enteral nutrition interactions were systematically searched for in the European Pharmacopoeia, Hagers Handbook of Pharmaceutical Practice, Birchers clinical-pharmacological data compilation, and the Martindale Complete Drug Reference, as well as from databases including DrugBank, DrugDex, PubChem, Google Scholar, and PubMed. Of the drugs most commonly administered via feeding tubes in the present stroke patient cohort, bisoprolol, candesartan, and ramipril could be considered the least critical due to their overall favourable properties. Acetylsalicylic acid, amlodipine, hydrochlorothiazide, omeprazole and esomeprazole, simvastatin, and torasemide pose risks based on pH or light-dependent instability or proposed food effects. The most critical drugs to be administered via feeding tubes are considered to be furosemide, levodopa, and levothyroxine as they show relevant instabilities under administration conditions and substantial food effects; the latter two even possess a narrow therapeutic index. However, little information is available on drug-tube and drug-formula interactions. Feeding tube administration of medications turned out to be a highly complex process with several unmet risks. Therefore, investigations that systematically assess these risk factors using clinically relevant model systems are urgently needed.